Dr. Ron’s Research Review – March 27, 2013

© 2013

This week’s research review focuses on glycine for sleep.

A recent study showed that glycine improves the quality of sleep in partially sleep-restricted healthy volunteers Sleep was restricted to 25% less than the usual sleep time for three consecutive nights. Before bedtime, 3 g of glycine or placebo were ingested. In subjects given glycine, the visual analog scale data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. These observations were also found via the questionnaire, indicating that glycine improves daytime sleepiness and fatigue induced by acute sleep restriction. Personal computer performance test revealed significant improvement in psychomotor vigilance test. (Bannai, Kawai et al. 2012) (Bannai and Kawai 2012)

A previous a randomized double-blinded cross-over trial showed that glycine ingestion before bedtime improves sleep quality. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The glycine ingestion significantly improved the following elements: “fatigue”, “liveliness and peppiness”, and “clear-headedness”. (Inagawa, Hiraoka et al. 2006)

Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine's effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. (Bannai and Kawai 2012)

Dr. Ron


Articles

New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep

            (Bannai and Kawai 2012) Download

Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine's effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials.

The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers

         (Bannai, Kawai et al. 2012) Download

Approximately 30% of the general population suffers from insomnia. Given that insomnia causes many problems, amelioration of the symptoms is crucial. Recently, we found that a non-essential amino acid, glycine subjectively and objectively improves sleep quality in humans who have difficulty sleeping. We evaluated the effects of glycine on daytime sleepiness, fatigue, and performances in sleep-restricted healthy subjects. Sleep was restricted to 25% less than the usual sleep time for three consecutive nights. Before bedtime, 3 g of glycine or placebo were ingested, sleepiness, and fatigue were evaluated using the visual analog scale (VAS) and a questionnaire, and performance were estimated by personal computer (PC) performance test program on the following day. In subjects given glycine, the VAS data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. These observations were also found via the questionnaire, indicating that glycine improves daytime sleepiness and fatigue induced by acute sleep restriction. PC performance test revealed significant improvement in psychomotor vigilance test. We also measured plasma melatonin and the expression of circadian-modulated genes expression in the rat suprachiasmatic nucleus (SCN) to evaluate the effects of glycine on circadian rhythms. Glycine did not show significant effects on plasma melatonin concentrations during either the dark or light period. Moreover, the expression levels of clock genes such as Bmal1 and Per2 remained unchanged. However, we observed a glycine-induced increase in the neuropeptides arginine vasopressin and vasoactive intestinal polypeptide in the light period. Although no alterations in the circadian clock itself were observed, our results indicate that glycine modulated SCN function. Thus, glycine modulates certain neuropeptides in the SCN and this phenomenon may indirectly contribute to improving the occasional sleepiness and fatigue induced by sleep restriction.

Subjective effects of glycine ingestion before bedtime on sleep quality

(Inagawa, Hiraoka et al. 2006) Download

The effects of glycine on sleep quality were examined in a randomized double-blinded cross-over trial. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The glycine ingestion significantly improved the following elements: “fatigue”, “liveliness and peppiness”, and “clear-headedness”. These results suggest that glycine produced a good subjective feeling after awakening from sleep.

A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis

            (Melendez-Hevia, De Paz-Lugo et al. 2009) Download

In a previous paper, we pointed out that the capability to synthesize glycine from serine is constrained by the stoichiometry of the glycine hydroxymethyltransferase reaction, which limits the amount of glycine produced to be no more than equimolar with the amount of C 1 units produced. This constraint predicts a shortage of available glycine if there are no adequate compensating processes. Here, we test this prediction by comparing all reported fl uxes for the production and consumption of glycine in a human adult. Detailed assessment of all possible sources of glycine shows that synthesis from serine accounts for more than 85% of the total, and that the amount of glycine available from synthesis, about 3 g/day, together with that available from the diet, in the range 1.5-3.0 g/day, may fall significantly short of the amount needed for all metabolic uses, including collagen synthesis by about 10 g per day for a 70 kg human. This result supports earlier suggestions in the literature that glycine is a semi-essential amino acid and that it should be taken as a nutritional supplement to guarantee a healthy metabolism.


Glycine ingestion improves subjective sleep quality in human volunteers

            (Yamadera, Inagawa et al. 2007) Download

In human volunteers who have been continuously experiencing unsatisfactory sleep, effects of glycine ingestion (3 g) before bedtime on subjective sleep quality were investigated, and changes in polysomnography (PSG) during sleep were analyzed. Effects on daytime sleepiness and daytime cognitive function were also evaluated. Glycine improved subjective sleep quality and sleep efficacy (sleep time/in-bed time), and shortened PSG latency both to sleep onset and to slow wave sleep without changes in the sleep architecture. Glycine lessened daytime sleepiness and improved performance of memory recognition tasks. Thus, a bolus ingestion of glycine before bedtime seems to produce subjective and objective improvement of the sleep quality in a different way than traditional hypnotic drugs such as benzodiazepines.


References

Bannai, M. and N. Kawai (2012). "New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep." J Pharmacol Sci 118(2): 145-8 PMID: 22293292

Bannai, M., N. Kawai, et al. (2012). "The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers." Front Neurol 3: 61 PMID: 22529837

Inagawa, K., T. Hiraoka, et al. (2006). "Subjective effects of glycine ingestion before bedtime on sleep quality." Sleep and Biological Rhythms 4(1): 75–77 PMID:

Melendez-Hevia, E., P. De Paz-Lugo, et al. (2009). "A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis." J Biosci 34(6): 853-72 PMID: 20093739

Yamadera, W., K. Inagawa, et al. (2007). "Glycine ingestion improves subjective sleep quality in human volunteers." Sleep and Biological Rhythms 5(2): 126–131 PMID: